Self-healing elastomer system

A composite material includes an elastomer matrix, a set of first capsules containing a polymerizer, and a set of second capsules containing a corresponding activator for the polymerizer. The polymerizer may be a polymerizer for an elastomer. The composite material may be prepared by combining a first set of capsules containing a polymerizer, a second set of capsules containing a corresponding activator for the polymerizer, and a matrix precursor, and then solidifying the matrix precursor to form an elastomeric matrix

Cloning and Characterization of Subunits of the T-Cell Receptor and Murine Leukemia Virus Enhancer Core-Binding Factor.

Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core-binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds to core sites in murine leukemia virus and T-cell receptor enhancers. Affinity-purified CBF contains multiple polypeptides. In this study, we sequenced five tryptic peptides from two of the bovine CBF proteins and isolated three cDNA clones from a mouse thymus cDNA library encoding three of the tryptic peptides from the bovine proteins. The cDNA clones, which we call CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6, encode three highly related but distinct proteins with deduced molecular sizes of 22.0, 21.5, and 17.6 kDa that appear to be translated from multiply spliced mRNAs transcribed from the same gene. CBF beta p22.0, CBF beta p21.5, and CBF beta p17.6 do not by themselves bind the core site. However, CBF beta p22.0 and CBF beta p21.5 form a complex with DNA-binding CBF alpha subunits and as a result decrease the rate of dissociation of the CBF protein-DNA complex. Association of the CBF beta subunits does not extend the phosphate contacts in the binding site. We propose that CBF beta is a non-DNA-binding subunit of CBF and does not contact DNA directly

Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production

This is the peer reviewed version of the following article: Soukup, A. A., Chiang, Y.-M., Bok, J. W., Reyes-Dominguez, Y., Oakley, B. R., Wang, C. C. C., Strauss, J. and Keller, N. P. (2012), Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production. Molecular Microbiology, 86: 314–330. doi:10.1111/j.1365-2958.2012.08195.x, which has been published in final form at http://doi.org/10.1111/j.1365-2958.2012.08195.x. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Regulation of secondary metabolite (SM) gene clusters in Aspergillus nidulans has been shown to occur through cluster specific transcription factors or through global regulators of chromatin structure such as histone methyltransferases, histone deacetylases, or the putative methyltransferase LaeA. A multi-copy suppressor screen for genes capable of returning SM production to the SM deficient ΔlaeA mutant resulted in identification of the essential histone acetyltransferase EsaA, able to complement an esa1 deletion in Saccharomyces cereviseae. Here we report that EsaA plays a novel role in SM cluster activation through histone 4 lysine 12 (H4K12) acetylation in four examined SM gene clusters (sterigmatocystin, penicillin, terrequinone, and orsellinic acid), in contrast to no increase in H4K12 acetylation of the housekeeping tubA promoter. This augmented SM cluster acetylation requires LaeA for full effect and correlates with both increased transcript levels and metabolite production relative to wild type. H4K12 levels may thus represent a unique indicator of relative production potential, notably of SMs

Transcriptional Regulation of Chemical Diversity in Aspergillus fumigatus by LaeA

Secondary metabolites, including toxins and melanins, have been implicated as virulence attributes in invasive aspergillosis. Although not definitively proved, this supposition is supported by the decreased virulence of an Aspergillus fumigatus strain, ΔlaeA, that is crippled in the production of numerous secondary metabolites. However, loss of a single LaeA-regulated toxin, gliotoxin, did not recapitulate the hypovirulent ΔlaeA pathotype, thus implicating other toxins whose production is governed by LaeA. Toward this end, a whole-genome comparison of the transcriptional profile of wild-type, ΔlaeA, and complemented control strains showed that genes in 13 of 22 secondary metabolite gene clusters, including several A. fumigatus–specific mycotoxin clusters, were expressed at significantly lower levels in the ΔlaeA mutant. LaeA influences the expression of at least 9.5% of the genome (943 of 9,626 genes in A. fumigatus) but positively controls expression of 20% to 40% of major classes of secondary metabolite biosynthesis genes such as nonribosomal peptide synthetases (NRPSs), polyketide synthases, and P450 monooxygenases. Tight regulation of NRPS-encoding genes was highlighted by quantitative real-time reverse-transcription PCR analysis. In addition, expression of a putative siderophore biosynthesis NRPS (NRPS2/sidE) was greatly reduced in the ΔlaeA mutant in comparison to controls under inducing iron-deficient conditions. Comparative genomic analysis showed that A. fumigatus secondary metabolite gene clusters constitute evolutionarily diverse regions that may be important for niche adaptation and virulence attributes. Our findings suggest that LaeA is a novel target for comprehensive modification of chemical diversity and pathogenicity

Does Media Affect Learning: Where Are We Now?

It is time to extinguish the argument as to whether or not the media of 1983 could, should or would affect learning outcomes. The technological advances that have occurred in the 20 years since Clark sparked the debate and Kozma fanned the flames have made the question irrelevant. High-speed, portable, reasonably priced computers, the Internet, and the World Wide Web have changed the face of how, when, and where learning occurs. The media of 2004 does affect learning. The question is no longer if; the question is how

The Lantern Vol. 16, No. 3, Spring 1948

• Not So Light • Babba\u27s Luck • Winter Night • God Hath Wrought • Less Than Trivia • What is Progress? • Betrayal • The Key • Journey From a Star • War and Peace • Experiment in Prose Poetry • Dawn • Eternal Question • My Gift • Jazz Fantasy • M.W. Witmerhttps://digitalcommons.ursinus.edu/lantern/1045/thumbnail.jp

Molecular genetic analysis of the orsellinic acid/F9775 gene cluster of Aspergillus nidulans†,‡

F-9775A and F-9775B are cathepsin K inhibitors that arise from a chromatin remodelling deletant strain of Aspergillus nidulans. A polyketide synthase gene has been determined to be responsible for their formation and for the simpler, archetypical polyketide orsellinic acid. We have discovered simple culture conditions that result in the production of the three compounds, and this facilitates analysis of the genes responsible for their synthesis. We have now analysed the F9775/orsellinic acid gene cluster using a set of targeted deletions. We find that the polyketide synthase alone is required for orsellinic acid biosynthesis and only two additional genes in the cluster are required for F9775 A and B synthesis. Our deletions also yielded the bioactive metabolites gerfelin and diorcinol

Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

<p>Abstract</p> <p>Background</p> <p>Extracts of chicory root have anti-inflammatory properties <it>in vitro </it>and in animal models of arthritis. The primary objective of this investigator-initiated, Phase 1, placebo-controlled, double blind, dose-escalating trial was to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis (OA). Secondary objectives were to assess effects on the signs and symptoms of this disorder.</p> <p>Methods</p> <p>Individuals greater than 50 years of age with OA of the hip or knee were eligible for trial entry. A total of 40 patients were enrolled in 3 cohorts and were treated with escalating chicory doses of 600 mg/day, 1200 mg/day and 1800 mg/day for 1 month. The ratio of active treatment to placebo was 5:3 in cohorts 1 and 2 (8 patients) each and 16:8 in cohort 3 (24 patients). Safety evaluations included measurement of vital signs and routine lab tests at baseline and the end of the treatment period. Efficacy evaluations at baseline and final visits included self-assessment questionnaires and measurement of the 25-foot walking time.</p> <p>Results</p> <p>In the highest dose cohort, 18 patients who completed treatment per protocol were analyzed for efficacy. In this group, 13 patients showed at least 20% improvement in the defined response domains of pain, stiffness and global assessment: 9 of 10 (90%) patients randomized to active treatment with chicory and 4 of 8 (50%) patients randomized to placebo (P = 0.06). In general, the treatment was well-tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event.</p> <p>Conclusions</p> <p>The results of this pilot study suggest that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. Clinicaltrials.gov identifier: NCT 01010919.</p

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine